### Docket Number EPA-HQ-OPP-2014-0341 www .r egulations.gov



# Picaridin Combined Work Plan, and Proposed Interim Registration Review Decision

Approved by:

Date: 

# Case Number 7433 December 2014

# ~~p~~ Richard P. Keigwin,Jr. Director Pesticide Re-evaluation Division**/~-** 

# 9· -**~01~** •,i, •

### Table of Contents Contents I. 

### INTRODUCTI ON .. .. . .... . . .. .... ... ......................................... . .. . ................... 4 II. STATUTORY AND R EGULATORY AUTHORITY ...........................................4 III. PICARIDIN CHEMICAL FACTS . . .. . .. . .. .. .... . ....... .. ........ . .. . .................... . .. . . ... 5 IV . USE AND USAGE INFORMATION . . ........ ... ................ . ........................... .... 5 V . RECENT ACTIONS ........ ... .. . .. . ...... .. . ................... .. .. . .. .· . .. . .. . .. . ..... . .. .. .........6 VI. SCIENTIFIC ASSESSMENTS .......... . ........ . .. . ... ..... . ........ . .. . ................. .. . . . .. .. 6 A . Human H ealth Assessment .................................................................... . ... . ... ... . . . ... . ..... . ... . . . . . .. .............. 6 1. R.isk Conclusions .. . ............................................... . ........... ... ... ...... . ... .. ........ . ... ... ..... ...................... 6

- Hazard Characterization..... ....... ............ .. ............................. ............................................ . .. ...... 6

- Dietary Assessmen t . ...... . . ..... ...... ............. . .. .. . . . . ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ... . . . . . . . . . . . . . . . . . . . . . . ....... . ...... 6

- Residential Assessment ........................................................... ............... ................................... 7

- Occupational Assessmen t ................................................ . ....... ..... ... .. ...... ..... . ... . .... ...... . ............ 7

- Aggregate Assessment ......................................................................................... .............. ... ... .. 7 2 . Human Health Incidents ..... . . . . ... . ... ..... . ... .............. . .......... .. ........... . . . . . . . . ... . . . . . . . . . . . . . . . . . . . . . . . ... . . . . . . . . . 7 3. Food Tolerances ..... . . ...... . . ... .:. . . . . . . ... .................. . . . ... . . . . . . . . . . . ... . . . . . . . ... . . . . . . . . . . . . . . ... . ....... . ....... . . . . . . . . . . . . 7 B. Ecological Assessment ...... .............. ... . ... .............. ..... ... ................................................... . ................. . ..... 8 1. Environmental Fate and Exposure ........................................ .. .......... ........ ............................ .... 8 2 . R.isk Conclusions ... . ......... . ... ......... ................................ ... ............................................ ... . . ............ 8

- Aquatic Organisms . . . . . . . . .. ........................................ ..... . . . . . . . . . . . ... . ... . ... . . . . . . . . . . . . . . ... . ... . ........... . . . . . . . 8

- Terrest ri al Organisms .... . ....... . . . . . . . ........... : .......... . . ... . . . . . . . . . . . . . ... . ... . . . . . . . . . . . . . . . . . . ................. . . . . . . . . . . . 8 3. Ecological I ncidents ... ............. .................... ...... ... ....................................... ....... . ... . ......... ............ 8 

### C. Endangered Species Assessment ............................................ . ... . . ................... ................................ . . .... 9 D. Endocrine Disruptor Screening Program ...................................... ....... . ................. ................ :............ 9 V II. COMBINED WORKPLAN AND PROPOSED INTRERIM REGISTRATION REVIEW DECISION . . .. . . .. ... .. .. .. .. . .. .. . ............... .. . . .. . .. . .. . .. . .. . .. . .. . .. . ..... ..... . .. . ......... . 10

- Tolerance Ammendments .... .. ... . . .. . .. . ..... . .. . . . . .............. . .. . .. . .. . .. . .. . .. . .. . ..... . .. 10

- R.isk Mitigation and Rationale . . .. . .. ......... . .. .. . . . .... . .. . ...... ................ . . .. .. . .. . . .. . . 10 ,.;_ - Interim Registration Review Decision .. .. .... .. . .. . .................... . .. . .. . .. . .. . .. . ..... . .. .. 10 VIII. NEXT STEPS AND TIMELINE ..... .. . ..... . ........ . .. . .. . .. ... .......... . ........ .. . .. . ....... 10



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### References: T lus document summarizes the Env ironmental Prot ection Agency's current position based on the following documents:

1 . Preliminary Environmental rate and Ecological Risk Assessment for the Registration Review 

### of Picaridin. Brian Montague and Gabe Rothman. September 22, 20 1 4. 2. Picaridin Preliminary Human Health Risk Assessment in Support 

### of Registration Review. Karlyn Middleton and Zaida Figueroa . December 5, 20 1 4 . 3. Picaridin: Tier I Review 

### of Human Incidents. Elizabeth Evans and Sharma Recore. February 11, 2014 . 4. BEAD Chemical Profile for Registration Review: Picaridin. David Brassard, Cynthia Doucoure, and Derek Berwald . March 20, 20 1 4. These and other supporting documents for the picaridin registration review case may be found in the docket EPA - HQ - OPP- 2014 -0 341 at http://www. regulations.gov.



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### 1. INTRODUCTION The docket for picaridin is now open, initiating the first public comment period for this registration review (d ocket number EPA- HQ -OPP-2014-0341). The Environmental Protection Agency's ( EPA or the Agenc y) is issuing a combined Work Plan and Propos e d Interim Regis tration Review Decision along with Preliminary Ecological and Human He a lth Ri sk Assessments fo r picaridin pursuant to 40 CFR Section s 1 55 .50, 155 . 53, 155.56, and 155.58, f o llowed b y a sixty (60) day public comment peri od. This document explains what EPA's Office o f Pesticide Programs knows about picaridin, highlighting assessment needs and providing an anticipated timeline for completing picariclin 's review. These documents are being made available f or public comment fo r a sixty (60) day per iod and can found in the d ocket E PA-HQ-OPP-2014 -0341 at ht q1 : 

### I / www .rcgulnti o ns.gov. A registration review decision is the Agency's determination whether a pesticide m eets, or does not meet, th e standard for registration in the Federal In sec ticide, Fungicide, and Rodenticide Act (FIFRA). The Agency may issue, when it determines it to be appropriate, a proposed in terim reg i stra tion review d ecision before completing a registration review. Am ong other things, the proposed interim registration review decision may require new risk mitigation measures, impose interim risk mitigatio n measures, identify data or information required to complete the review, and include schedules fo r s ubmitting the required data, co nducting the new risk assessment and completing the registration review. Picariclin is a broad-spectrum in sect repellent re gistered for use against biting flies, chiggers, fleas, mosquitoes, and ticks . Picaridin is lab eled for use on h uman skin and footwear. There is also one registered p r oduct for use on horses. Picariclin was first registered in the U nited States in 2000. Picaridin i s not regis tere d for any agricultural, non -agricultural, or greenhouse applications. For further information about picariclin, additional documents can be found in E P A's public docket (EP A - HQ -OPP -2014-0341) at W\Vw.regulations.gov. 

### II. STATUTORY AND REGULATORY AUTHORITY The Food Quality Protection Ac t (FQPA) of 1996 mandated a registration review program . A ll pes ticides distrib uted o r sold in the U.S. gene rally must be regis tered by EPA, based on scientific data showing that they will not cause unreasonable risks to human health or the environment when used as directed on product labeling . Th e regi stration review p r ogram i s intended to make sure that, as the ability to asse ss risk e volves and as polic ies and practices change, all registered pesticide s continue to meet th e statutory standard of no unreasonable adverse effects to human health or the environment. Change s in science, public policy, and pesticide use practices will occur over time. Through the registration review program, the Agency periodically reevaluates pesticides to make sure that as change occurs, products in the marketplace can b e used safely. Information on this program is provided at ww w .c pa.gov /op p srrdl /registration review/. Th e Agency is imp lementing the registratio n review program pursuant to Section 3(g) of F I FRA, and will review each registered p esticide every 15 years to determine whether it continues to meet the FIFRA standard for registration. The regulations governing regis tratio n review begin at 40 CFR 155.40. The Agency will consider benefits in formatio n and data as requited by FIFRA . The public phase of registratio n review begins when the initial docket is opened for each case. The 4docket is the Agency's opportunity to state what it knows about the pesticide and what additional risk analyses and data or information 

### it believes are needed to make a registration review decision . III. PICARIDIN CHEMICAL FACTS Table 1: Chemical f acts for Pica ridin PC code 070705 Case Number 7433 CAS Number 1 1 9515 - 38 -7 Year fl.rst registered 2000 Pesticide Type Insect repellent Chemical class Piperidine Reregistration Eligibility Because it was registered after November 1 984, picaridin was not Decision (RED) subject to reregistration. Tolerance Reassessment Not applicable Eligibility Decision (IRED) Cumulative group Not applicable. The Agency has not de termined that picaridin shares a common mechanism of toxicity with other chemical substances . 40 CFR Citation There are no registered p icaridin food/feed uses and no established tolerances for picaridin Dual- use Conventional pesticidal uses only Non -pesticidal uses No non - pesticida l uses of picar idin Pesticide Re - evaluation Ricardo Jones, jones .ricardo@epa .gov, (703) 347-0493 Division, Chemical Review Manager Registration Division, Kevin Sweeney, sweeney .kevin@epa .gov, (703) 305-5063 Product Manager IV. USE AND USAGE INFORMATION Picaridin is reported to be widely used by consumers as an insect repellant. Picaridin is an alternative to DEET and is second after DEET in total U .S. use. Available data on picaridi.n show that it accounted for the 15% of total insect repellant consumption in 2009, and 14.33% of total consumption in 20 1 1 (EPA Proprietary Data, 2010 and 2012). The use of insect repellents such as picaridin is intended to provide personal and public health benefits. Application of picaridin ins ect repellents to the skin is intended to help prevent bites from mosquitoes, ticks and other biting insects that may vector diseases such as Lyme disease, West Nile virus, malaria, yellow fever, dengue fever, and encephalitis. See the 

### BEAD Chemical Profile for Registration Retliew: Pi c aridin in the registration review docket for more details . Summary of Use Table 2: P icaridin Use and U s age I n formati o n 

# IFor use on the human body and on horses to rep el mosquitos, ticks,

biting flies, deer flies, gnats , no - see -urns, chiggers and fleas . 5Use Sites Picaridin is registered for use on human skin, hair, footwear, and horses. Summary of Usage Approximat ely 2.2 million lbs. of active ingredient were used in 2009, and 2 . 1 million lbs . in 2011. Formulation Type(s) Formulations include aerosol or pump spray, towelettes/wipe, and cream/lotion. Application Method(s) Pi.caridin i.s generally applied using aerosol sprays, non-aerosol sprays, creams, lotions , and towelett es. Technical Registrant(s) Lanxess Corporation (39967) No. of Registrations 28 - FIFRA Section 3 registrations Restricted Use No 

### V. RECENT ACTIONS There are no recent registration actions for picaridin. 

### VI. SCIENTIFIC ASSESSMENTS A. Human Health Assessment The human health exposure and toxicological database 

### is adequate for registration review of picaridin. The Agency does not need additional studies in order to characterize the human health exposure, hazard and risk from picaridin . Because no additional human health or toxicity data are needed for the registration review of picaridin, the Agency has determined that it is appropriate to conduct a preliminary human health risk assessment for picaridin. A summary of the Agency's preliminary human health risk assessment is p resented below. For detailed discussions see: Picaridin Preliminary Human Health RiskAmssment in Support 

## of Registration Review, dated December 5, 2014, in the public docket (EPA - HQ -OPP-20 1 4- 0341) which can be accessed at W \ V\v .regulati ons .go Y. 1. 

### Risk Conclusions I - :lazard Charaderization In p revious assessments the Agency identified toxicological endpoints for picaridin. However, new toxicological data fo r picaridin indicate that the primary toxicological effects (in the kidney) observed in oral and dermal toxicity studies in rates are species specific, and are not relevant for humans . In addition, the Agency has reviewed the picaridi..n data base and using a weight-ofevidence approach, (i.e., considering physical, chemical characteristics, use and exposure), has determined that neither inhalation to xicity nor immunotoxicity data are required for picaridin (Hazard and Science Policy Council (HASPOC) 

### 1XR# 0056905; Feb ., 2013) . Therefore, with no toXicological endpoints identified in the hazard database, a qualitative human health analysis i s considered appropriate for picaridin. Dietary Assusment Picaridin is not registered for any food or · feed uses, and its use is not expected to contaminate drinking water; there fore no dietary (for or drinking water) analysis was completed.



### 6ResidentialAssessment Picaridin is registered for use directly on human skin. Picaridin products can be applied several times in one day, and used for several days, weeks or longer depending on the personal activity pattern and/or geographic area . Use is expected to result in both dermal and inhalation exposure, as well as incidental oral (hand-to-mouth) exposure . However, the toxicity datab ase indicated no endpoints applicable to the oral, dermal, or inhalation routes of exposure. Therefore, a residential assessment for picaridin was not completed OccupationalAssessment There is no occupational exposure associated with registered uses of picaridin . Therefore an occupational assessment for picaridin was not completed. Aggregate Assessment Because neither a dietary or residential assessment were completed, an aggregate assessment for picaridin was not completed. 

### 2. Human Health Incidents The Office of Pesticide Programs (OPP) Incident Data System (IDS) was used to retrieve pesticide incident data on picaridin . T he IDS records incidents in one of two modules: Main IDS and Aggregate IDS . Main IDS contains incidents resulting in higher severity outcomes and provides more de tail with regard to case specifics . Aggregate IDS contains incidents resulting in less severe human incidents (minor , unknown, or no effects outcomes). From January 1, 2009 to J anuary 15, 2014, there were 26 incidents involving picaridin reported in the database. These incidents were classified as moderate sever ity, not life threatening and the person returned to his/her pre-exposure state of health wit h no additional res idual disability . In the Aggregate IDS, from January 1, 2009 to January 15, 20 1 4, there were 214 reported incidents involving picaridin. These incidents were classified as minor severity**a~d** the symptoms resolved rapidly and usually involved skin, eye or respiratory irritation. The Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health (CDC/NIOSH) Sentinel Event Notification System for Occupational Risk-Pesticides (SENSOR) databases were also queried . The NIOSH SENSOR- Pesticides 1998-2010 data identified 22 cases involving picaridin, 19 involving a single active ingredient and three involving multiple active ingredients. Of the 19 cases involving the single active ingredient, 18 cases were low in severity, largely involving dermal or eye irritation . One case was moderate in severity, and involved direct application of a product containing picaridin to the face of an infant. Reports of adverse health effects allegedly due to a specific pesticide exposure (i .e . , an "incident") are largely self -reported and therefore, generally speaking, neither exposure to a pesticide or reported symptom (or the connection between the two) is validated or otherwise confirmed. Typically, causation cannot be determined based on incident data (Picaridin Preliminary Human Health Risk Assessment in Support 

## of Registration Review, dated December 5, 2014) . · 

### 3. Food Tolerances There are no U.S. tolerances established for picaridin because picaridin is not registered for any food or feed uses. 

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### B. Ecological Assessment The ecological fate and ecotoxicity database is considered adequate for the registration review of picaridin. The Agency does not need additional studies in order to characterize the ecological exposure or hazard from picaridin . Because neither ecolog ical fate nor toxicity data are needed for the registration review of picaridin, the Agency has determined that it is appropriate to conduct a preliminary ecological risk assessment for picaridin. A summary of the Agency's preliminary ecological risk assessment is presented below. For detailed discussions see Preliminary EntJironmental Fate and Ecological Risk Asmsment for the Registration Review 

## of Picaridin, dated September 22, 2014, in the public docket (EPA-HQ-OPP-2014-0341) which can be accessed at www. rcgul ations .g<w . The Agency has completed a screening -level endangered and threatened (listed) species assessment for picar idin. The Agency is currently working with its federal counterparts and other stakeholders to implement an interim approach for assessing potential risk to listed species and their designated critical habitats. Once the scientific methods necessary to complete risk assessments for listed species and their designated critical habitats are fmalized, the Agency will complete its endangered species assessment for picaridin. Based on its registered use pattern, the Agency does not anticipate listed terrestrial species to come into contact with picaridin . Also, based on a conservative analysis, estimated risk quotients for aquatic species are far below levels of concern (LOCs). Therefore, the Agency anticipates making a "no effects" determination under the E ndangered Species Act (ESA) for all listed species, and no adverse modification of designated critical habitat for such species is**exp~cted,** unless information provided to the Agency leads to a change in this anticipated determination. 

### 1. Environmental Fate and Exposure Picaridin is relatively stable, highly soluble in water, and does not easily volatilize. Based on tl1e use pattern and environmental fate properties of picaridin, significant environmental exposure (terrestr ial or aquatic) is not expected . 

### 2. Risk Conclusions Aquatic Organisms The Agency estimated potential exposure and acute risk to aquatic organisms. The Agency com pleted conservative exposure estimates, and res ulting acute risk quotients (R.Qs) are far below the Agency's level o f concern. While chronic RQs were not estimated, given the large margin of safety observed for acute effects, the Agency believes it unlikely that chronic risks would approach concern levels. SinWarly, risk to aquatic plants is presumed to be below the level of concern based on picaridin's low toxicity and low potential to en ter aquatic environments. Terrestrial Organisms Based upon the use pattern of picaticlin, the Agency does not expect a terrestrial exposure pathway to exist, and therefore , no terrestrial risk analysis was conducted. 

### 3. Ecological Incidents There are no reported incidents involving picaridin. A review of all available information in the following databases was completed in March 2014: Ecological Incident Information System 8(EllS), Aggregate Incident Reports database, Avian Monitoring Information System (AIMS), the Contaminant Exposure and Effects - Terrestrial Vertebrate (CEE-TV), or the OPP Incident Da ta System (IDS). For additional discussion of the reported ecological incidents, see the Preliminary Environmental Fate and Ecological Risk Asses sment for the Registration Review rfPicaridin. 

### C. Endangered Species As s es sment Based on the lack of exposure potential, and low risk potential of picaridin, the Agency concludes that effects on the environment are not reasonably expected to occur f rom the registered use of picaridin. Therefore, the EPA anticipates making a "no effects" determination under the Endang ered Species Ac t (ESA) for all listed species and that no adverse modification of de signat ed critical habitat for such species is expected from the registered use of picaridin, unless information provided to the Agency leads the Agency to change its anticipated determination. 

### C. Endocrine Disruptor Screening Program As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potentia l adverse outcomes from exposure to chemicals . Collectively, th ese studies include acute, subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, reproductive, and general or systemic toxicity . These studies include endpoints which may be susceptible to endocrine influence, including effects on endocrine target organ his topatholog y , organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, E PA evaluates acute tests and chronic studies that assess growth, developmental and reproductive ef fects in different taxonomic groups. As part of its most recent registration decision for picaridin, E PA reviewed these data and determined that a qualitative toxicity assessment is appropriate for picaridin . However, as required by FFDCA section 408(p), p icaridin is subject to the endocrine screening part of the Endocrine Disrupter Screening . Program (EDSP). EPA has developed the EDSP to determine whether certain substances (including pesticide active and other ingredients) may have an effec t in humans or wildlife similar to an effect produced by a "naturally occurring estrogen, or other such endocrine effects as the Administrator may designate . " The EDSP employs a two -tiered approach to making the statUtorily required determinations . Tier 1 consists of a battery of 11 screening assays to identify the potential of a chem ical substance to interact with the estrogen , androgen, or thyroid (E, A, or T) hormonal systems . Chemicals that go through T ier 1 screening and are found to have the potential to interact w ith E, A, or T hormonal systems will proce ed to the next stage of the EDSP where EPA will determine which, if any, of the T ier 2 tests are n ecessary based on the available data. T ier 2 testing is designed to identify any adverse endocrine-related effects caused by the substance, and establish a dose -response relationship between the dose and the E, A, or T effect. · Under FFDCA section 408(p), the Agency must screen all pesticid e chemicals. Between October 2009 and February 2010, EPA issued test orders/data call-ins for the fust group of 67 ch emicals, which contains 58 pesticide active ingredients and 9 inert ingredients . A second list of

9chemicals identified f or EDSP screening was published on June 14, 2013 1 and includes some pesticides scheduled for Registration R eview and chemicals found in water. Neither of these lists should be construed as a list of known or likely endocrine disrupters. For further information on the status of the EDSP, the policies and procedures, the lists of chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our website. 2 In the interim, EPA 

### is making no human health or environmental safety findings associated with the E DSP screening of picaridin. Before completing this Registration Review, the Agency will make an EDSP FFDCA section 408(p) determination. 

### VII. COMBINED WORK PLAN AND PROPOSED INTERIM REGISTRATION REVIEW DECISION Tolerance AmendmentJ There are no U .S . tolerances established for picaridin, and so the Agency will not pursue any tolerance actions with picaridin. RiJk Mitigation and Rationale The Agency has identified no human health or ecological risks associated with registered uses of picaridin. Therefore , the Agency did not identify the need to modify the current registered use of picaridin. Interim RegiJtration Rev iew DeciJion In accordance with 40 CFR Sections 155.5 0, 155 .53, 155.56, and 155.58, the Agency is i ssuing this combined Work Plan and Proposed Interim Registration Review Decision along with Preliminary Hwnan Health and Ecological Risk Assessments . Excep t for the E DSP component of the picaridin registration review case, the Agency has made the following interim decision: (1) no additional data are required at this time;**a~d** (2) no changes to the affected picaridin registrations or their labeling are needed at this time. Currently registered uses of picaridin are not expected to result in adverse effects fo r listed and non-listed species, or critical habitat. As such, EPA expects to conclude ''no effect" for listed species and no adverse modification of designated critical habitat for all currently registered uses of picaridin, unless information provided to the Agency leads the Agency to change 

### its anticip ated determination. 

### VIII. NEXT STEPS AND TIMELINE A Federal Register Notice will announce the availability of this combined Work Plan, Proposed Interim Registration Review Decision, and Preliminary Ecological and human H ealth Risk Assessments for picaridin and allow a 60- day comment period for this combined document as well as the two preliminary risk assessments. If there are no significant comments or additional information submitted to the docket during the comment period that leads the Agency to change its proposed decision, EPA may issue an Interim Registration Review Decision for picaridin (case 7433). However, a fmal decision for picaridin may be issued without having previously issued an

1 See http: //www.re gul ations.go v /# !documentDetaii:D= EPA -H Q-OPPT-2009-0477 -0074 for the final second list of chemicals. 2 http ://www.epa.gov/ endo/ 

### 1 0interim decision. A final decision on the picaridin registration review case will occur after an EDSP FFDCA section 408(p) determination has been made. EPA h as created t he following estimat ed timeline for the com ple ti o n of picaridin's registration review. 

### Registration 

### Review f o r Picaridin- Proje c ted Registration Review Timeline A c tivities Es timated Date Open Public D ocket and Public Comment Period for Combined Work 20 1 4 - December P lan, and Proposed In terim Registration Review Decision along with Preliminary Human Health and Ecological Ri sk Assessments C lo se Public Comment Period 2014- February Interim Registration Review D ecision and B egin Post- Decision Follow- 2014 - June up3 Total(years) 0.5

3 A final dec ision on the picarid in registration review case, in accordance with 40 CFR Section 155.158, w ill occur a fter an E DSP FFDC A sect ion 408(p) detennination has been made. 

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